1xhn
From Proteopedia
(New page: 200px<br /> <applet load="1xhn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xhn, resolution 1.95Å" /> '''The crystal structu...) |
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| - | [[Image:1xhn.gif|left|200px]]<br /> | + | [[Image:1xhn.gif|left|200px]]<br /><applet load="1xhn" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1xhn" size=" | + | |
caption="1xhn, resolution 1.95Å" /> | caption="1xhn, resolution 1.95Å" /> | ||
'''The crystal structure of Cellular Repressor of E1A-stimulated Genes (CREG)'''<br /> | '''The crystal structure of Cellular Repressor of E1A-stimulated Genes (CREG)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The cellular repressor of E1A-stimulated genes (CREG) is a secreted | + | The cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein that inhibits proliferation and enhances differentiation of human embryonal carcinoma cells. CREG binds to the cation-independent mannose 6-phosphate (M6P)/insulin-like growth factor II (IGF2) receptor (IGF2R) (M6P/IGF2R), and this receptor has been shown to be required for CREG-induced growth suppression. To better understand CREG function in cellular growth and differentiation, we solved the 3D crystal structure of this protein to 1.9-A resolution. CREG forms a tight homodimeric complex, and CREG monomers display a beta-barrel fold. The three potential glycosylation sites on CREG map to a confined patch opposite the dimer interface. Thus, dimerization of glycosylated CREG likely presents a bivalent ligand for the M6P/IGF2R. Closely related structural homologs of CREG are FMN-binding split-barrel fold proteins that bind flavin mononucleotide. Our structure shows that the putative flavin mononucleotide-binding pocket in CREG is sterically blocked by a loop and several key bulky residues. A mutant of CREG lacking a part of this loop maintained overall structure and dimerization, as well as M6P/IGF2R binding, but lost the growth suppression activity of WT CREG. Thus, analysis of a structure-based mutant of CREG revealed that binding to M6P/IGF2R, while necessary, is not sufficient for CREG-induced growth suppression. These findings indicate that CREG utilizes a known fold for a previously undescribed function [corrected] |
==About this Structure== | ==About this Structure== | ||
| - | 1XHN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1XHN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XHN OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Cygler, M.]] | [[Category: Cygler, M.]] | ||
| - | [[Category: Lunin, V | + | [[Category: Lunin, V V.]] |
[[Category: Sacher, M.]] | [[Category: Sacher, M.]] | ||
[[Category: beta-barrel]] | [[Category: beta-barrel]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:54:54 2008'' |
Revision as of 13:54, 21 February 2008
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The crystal structure of Cellular Repressor of E1A-stimulated Genes (CREG)
Overview
The cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein that inhibits proliferation and enhances differentiation of human embryonal carcinoma cells. CREG binds to the cation-independent mannose 6-phosphate (M6P)/insulin-like growth factor II (IGF2) receptor (IGF2R) (M6P/IGF2R), and this receptor has been shown to be required for CREG-induced growth suppression. To better understand CREG function in cellular growth and differentiation, we solved the 3D crystal structure of this protein to 1.9-A resolution. CREG forms a tight homodimeric complex, and CREG monomers display a beta-barrel fold. The three potential glycosylation sites on CREG map to a confined patch opposite the dimer interface. Thus, dimerization of glycosylated CREG likely presents a bivalent ligand for the M6P/IGF2R. Closely related structural homologs of CREG are FMN-binding split-barrel fold proteins that bind flavin mononucleotide. Our structure shows that the putative flavin mononucleotide-binding pocket in CREG is sterically blocked by a loop and several key bulky residues. A mutant of CREG lacking a part of this loop maintained overall structure and dimerization, as well as M6P/IGF2R binding, but lost the growth suppression activity of WT CREG. Thus, analysis of a structure-based mutant of CREG revealed that binding to M6P/IGF2R, while necessary, is not sufficient for CREG-induced growth suppression. These findings indicate that CREG utilizes a known fold for a previously undescribed function [corrected]
About this Structure
1XHN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The crystal structure of CREG, a secreted glycoprotein involved in cellular growth and differentiation., Sacher M, Di Bacco A, Lunin VV, Ye Z, Wagner J, Gill G, Cygler M, Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18326-31. Epub 2005 Dec 12. PMID:16344469
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